Computerized Training Improves Cognition in Schizophrenia

An intensive computerized cognitive-training program that targets perceptual impairments such as auditory processing in patients with schizophrenia can substantially improve verbal learning and memory, which may then allow for gains in “real-world” functioning, according to a new study.
The 50-hour “restorative” neuroplasticity-based program includes increasingly complex auditory working memory and verbal learning exercises that incorporate frequent rewards in the form of points and animation.
Carried out in collaboration with basic neuroscientist Michael Merzenich, PhD, a leading researcher in learning-inducedbrain plasticity mechanisms, with software developed by Posit Science, the study is published in the July issue of theAmerican Journal of Psychiatry.

Clearer Signal
Accurate processing of the elements of auditory and verbal information is necessary for the brain to perform higher order verbal cognitive operations such as manipulating information in working memory, encoding, and retrieval, said
study author Sophia Vinogradov, MD, from the University of California, San Francisco. “It’s like improving the tuning on a radio with a lot of static — if you can get a clearer signal, you can process more of the information,” she told
Medscape Psychiatry. Patients with schizophrenia have abnormalities in frontotemporal cortical networks during verbal working memory, word encoding, and word recognition. They also experience disturbances at the earliest stages of auditory processing.

Critical Window

Cognitive training likely can open up a “critical window” to improve day-to-day functioning among patients with
schizophrenia, said Dr. Vinogradov. “With the brain operating more efficiently after training, it is more receptive to
various rehabilitative approaches such as supported employment or social-skills training,” she added.
The study included chronically ill but clinically stable patients with schizophrenia who were recruited from community mental-health centers and outpatient clinics. After baseline assessments, the subjects were randomly assigned to either the intervention or to a control group that involved playing computer games. Of the 55 subjects included in this study, 29 (20 men and 9 women) were assigned to the intervention group and 26 (20men and 6 women) to the control group. Some did the intervention at home and others in the laboratory. At baseline, there was no difference between the intervention and control groups on the Positive and Negative Syndrome Scale (PANSS), the Quality-of-Life Scale–Abbreviated Version, or in baseline cognitive performance.

Repetitive Exercises
Patients in the intervention group accessed the cognitive program 1 hour a day, 5 days a week, for an average of 10
weeks. The program consists of 6 repetitive exercises that use various frequencies and intervals common to everyday
speech to improve the speed and accuracy of auditory information processing.
“The rationale is that, in order to understand and remember verbal information, the brain must first generate precise and reliable neurological responses that represent the frequency, the timing, and the complex sequential relationships between speech sounds,” the authors write. The program continually and automatically adjusts the difficulty level to the user’s performance to maintain an approximately 85% rate of correct responses. This helps to keep the user engaged by maintaining a constant level of challenge. While the control group completed this cognition training, the control group played 16 standard computer games for the same time period. The control group was monitored by staff in the same manner as the subjects in the training session.Durable Effect at 6 Months
The study found a large overall improvement in a standardized measure of global cognition (effect size (d) = 0.86)
among patients in the training group. Compared with control subjects, those who received the training showed about a half-standard-deviation improvement in verbal learning and memory. The effect of the site (lab or home) did not make a difference. Individual patients, however, showed wide variation in their ability to make reliable gains in the auditory training exercises. In a separate study, the researchers followed some of the study subjects to 6 months and found that many maintained their cognitive gains, even though they had no further cognitive training. “That’s very promising,” said Dr. Vinogradov. It is likely that most individuals with schizophrenia could benefit from this cognitive-training program, except perhaps those with very low IQs or with such severe symptoms that they would find it difficult to engage in daily training, said Dr. Vinogradov.

Medications May Reduce Impact
However, some medications may interfere with response to the program. In related research, Dr. Vinogradov and her
colleagues found that medications with anticholinergic effects may reduce the impact of the training process.
“The implication here is that the medications that people take may affect their brain’s capacity to make use of this
training; and the corollary of this is that we may be able to come up with pharmacological interventions that enhance
the response to training,” she said. The researchers did not find any significant quality-of-life improvements immediately after subjects finished the 10 weeks of training but noted that improvements in community functioning may take time to manifest. One of the next steps for Dr. Vinogradov and her colleagues is to test the cognitive-training program in the community. They are planning another study in a downtown community mental-health setting. This study will randomly assign subjects with schizophrenia to either cognitive training plus supported employment or to the computer-games control condition plus supported employment. “Our belief is that cognitive-training exercises can boost the cognitive capacities of subjects, but then they need to be able to move into a skills-training setting where, with improved cognition, they’re better able to make use of learning opportunities such as vocational rehabilitation,” she said.Daily Challenges
In a related editorial, Michael F. Green, PhD, from the Semel Institute at the University of California, Los Angeles, also
addresses the issue of whether this training intervention can be adapted to the “real-world” environment.” Although we talk about cognition-enhancing drugs or cognitive remediation, the missing factor being sought is something that helps individuals learn and acquire skills to enable them to navigate their world and cope with life’s daily challenges.”

Dr. Green stresses that a basic cognition-enhancing strategy has to be combined with the teaching of psychosocial
skills and strategies to improve patients’ lives. This and other recent studies have added important new information about the role of cognitive interventions in schizophrenia, says Dr. Green. “There were fundamental concerns about whether the cognitive interventions that were primarily developed for brain-injured patients could be productively applied to patients with schizophrenia. Not any more.”

Dr. Merzenich is chief scientific officer of and holds stock options in Posit Science. The other authors report no
competing Interests. Dr. Green has served as a consultant to Abbott Laboratories, Astellas, GlaxoSmithKline,
Lundbeck, Otsuka, and Wyeth and served as a speaker for Janssen-Cilag in 2008–2009.